Tumorigenesis involves a series of cellular changes that progressively transform normal cells into malignant cancer cells. The goal of this program of basic research is to understand in molecular detail the cellular changes that lead to tumorigenesis. To identify these changes, program members study the regulation of DNA replication, gene expression, cell growth and transformation, and apoptosis, in normal and cancer cells. To probe the changes that normal cells undergo in the process of becoming cancer cells, the program uses a combination of cellular and viral experimental paradigms, including DNA tumor viruses and the response of cells to these viruses. These model experimental paradigms are addressed through a coordinated, multidisciplinary program of research in the fields of genetics, molecular and cell biology, and biochemistry. The program is closely integrated, consisting of eight interrelated research projects and three cores, which promote the research activities conducted in the scientific projects.